Do defects in axonal transport play a causative or contributory role in the neurodegeneration associated with the development of Alzheimer's disease (AD)? More specifically, do reductions in retrograde axonal transport suppress amyloid beta production and plaque deposition in mouse models of AD? Others in our lab have shown this to be the case in Drosophila, so I would like to test this hypothesis in mammals. My specific questions are: A) Does the reduction of dynein function suppress the axonal blockage phenotype observed in transgenic amyloid precursor protein (APP) mice? B) Are amyloid beta production and plaque deposition suppressed in these mice? I will address these questions by using two systems: 1) primary hippocampal cell cultures and 2) a Cre/Lox dynein heavy chain shDNA transgenic mouse model. If my experimental hypothesis holds true, these findings can contribute to the development of future novel therapeutic opportunities for AD. [unreadable] [unreadable]